A MYCN-independent mechanism mediating secretome reprogramming and metastasis in <i>MYCN</i> -amplified neuroblastoma-Reference-Cited by-同舟云学术

A MYCN-independent mechanism mediating secretome reprogramming and metastasis in MYCN -amplified neuroblastoma

Published:2023-08-25 Issue:34 Volume:9 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Zhang Hai-Feng¹²^ORCID,Delaidelli Alberto¹²,Javed Sumreen³,Turgu Busra¹²^ORCID,Morrison Taylor²^ORCID,Hughes Christopher S.¹²^ORCID,Yang Xiaqiu²,Pachva Manideep¹²,Lizardo Michael M.¹²,Singh Gurdeep²^ORCID,Hoffmann Jennifer⁴^ORCID,Huang Yue Zhou²^ORCID,Patel Khushbu⁴⁵^ORCID,Shraim Rawan⁴⁶,Kung Sonia H. Y.⁷^ORCID,Morin Gregg B.⁸⁹^ORCID,Aparicio Samuel¹²,Martinez Daniel⁴⁵^ORCID,Maris John M.⁴⁵^ORCID,Bosse Kristopher R.⁴⁵^ORCID,Williams Karla C.³^ORCID,Sorensen Poul H.¹²^ORCID

Affiliation:

1. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T1Z4, Canada.

2. Department of Molecular Oncology, BC Cancer Agency, Vancouver, BC V5Z1L3, Canada.

3. Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada.

4. Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

5. Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.

6. Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

7. Vancouver Prostate Centre, Vancouver, BC V6H3Z6, Canada.

8. Canada’s Michael Smith Genome Sciences Centre, Vancouver, BC V5Z4S6, Canada.

9. Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T1Z4, Canada.

Abstract

MYCN amplification ( MNA ) is a defining feature of high-risk neuroblastoma (NB) and predicts poor prognosis. However, whether genes within or in close proximity to the MYCN amplicon also contribute to MNA + NB remains poorly understood. Here, we identify that GREB1 , a transcription factor encoding gene neighboring the MYCN locus, is frequently coexpressed with MYCN and promotes cell survival in MNA + NB. GREB1 controls gene expression independently of MYCN, among which we uncover myosin 1B ( MYO1B ) as being highly expressed in MNA + NB and, using a chick chorioallantoic membrane (CAM) model, as a crucial regulator of invasion and metastasis. Global secretome and proteome profiling further delineates MYO1B in regulating secretome reprogramming in MNA + NB cells, and the cytokine MIF as an important pro-invasive and pro-metastatic mediator of MYO1B activity. Together, we have identified a putative GREB1-MYO1B-MIF axis as an unconventional mechanism promoting aggressive behavior in MNA + NB and independently of MYCN.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/sciadv.adg6693

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